Systemic sclerosis, or scleroderma (SSc), is characterized by three features: increased extracellular matrix accumulation in the skin and organs, vascular injury and tissue ischemia, and immune cell activation and autoantibody production. The disease is one of a class of connective tissue diseases including polymyositis, systemic lupus erythematosis, and rheumatoid arthritis, which all share some common immunological features and are sometimes found within families.
Several studies show specific HLA patterns associated with autoantibody production (1). However, family studies in the general population show only a weak genetic predisposition to scleroderma. One exception to this has been described for Choctaw Native Americans (2). This group has a high prevalence of scleroderma (469/100,000) and an HLA DR2 haplotype that is strongly associated with the disease. Preliminary mapping suggests that there may be a defect in the fibrillin gene (3), which is also thought to be defective in one of the few animal models for scleroderma, that of the mutant mouse line, Tsk-1 (4,5).
While the disease may have an underlying genetic basis in some cases, in the general population it is a complex trait that involves genetic risk factors and, in some cases, may also involve environmental toxins (6,7). New methods of treating scleroderma and related conditions would be very useful.